Cisplatin（CDDP）の血清・髄液中動態—Etoposide（VP−16）とCisplatinを併用した悪性神経膠腫に対する選択的動注療法と転移性脳腫瘍における静・動注療法との比較

Pharmacokinetics of Plasma and Cerebrospinal Fluid Cisplatin in Patients with Malignant Glioma and Metastatic Brain Tumor after Selective Intraarterial or Intravenous and Intracarotid Administration of Etoposide and Cisplatin

I．はじめに

　悪性脳腫瘍に対する化学療法については，抗癌剤の癌細胞に対する感受性，腫瘍領域での分布なども臨床的効果を左右する因子であり，cisplatinについてもその中枢神経における分布が報告されている^18,22）．これらの分布以外に髄液への移行は，髄腔内播種を示す悪性腫瘍細胞に対しても，またcisplatin投与による痙攣発作^18,24）などの中枢神経に対する副作用の観点からも重要であり，投与経路として静注法では，正常動物を用いた実験^11）や，あるいは1例のglioblastoma^1），neuroblastoma^5）や再発ependymomaの小児例^6），大量の放射線照射後のprimary germcell tumor^9）などからの臨床報告があるが，まとまった臨床報告はない．またcisplatin^7,14,17）やetoposide^8,21）の動注経験が報告され，それぞれの副作用・安全性について論じられており，最近ではMadajewiczら^16）のetoposideとcisplatinの併用動注の効果，toxicityについて報告されているが，やはり髄液への移行はまだ報告を見ない．今回私たちは現在施行している悪性神経膠腫に対するetoposideとcisplatin併用によるマイクロカテーテルを使用した超選択的動注療法^19）の治療時における血清，髄液濃度を調べ，platinum（以下Ptと記す）の動態を調べるとともに転移性脳腫瘍におけるcisplatin療法での静注あるいは頸動脈動注例の髄液移行と比較検討した．

CSF and plasma platinum levels were examined in patients with malignant glioma after administration of etoposide and cisplatin each at doses of 60mg/m² by 60-minute selective intraarterial infusion. These same factors were also examined in patients with metastatic brain tumors after administration of cisplatin at a doseof 60 or 100mg/m^{2 by 60-minute intracarotid or in-travenous infusion. Plasma and CSF samples taken through an Ommaya reservoir placed in the lateral ven-tricle or postoperative cavity were analyzed for plati-num content by atomic absorption spectroscopy. Plas-ma and CSF platinum levels were dose dependent. The overall plasma platinum curves were biphasic, with mean half-lives of 35 minutes and 56 hrs. The mean peak total CSF concentration was 10.0% of the peak total plasma platinum and 20.2% of the peak free plas-ma platinum in patients with malignant glioma. In pa-tients with a solid metastatic brain tumor, the mean peak total CSF concentration was 1.9% of the peak tot-al plasma platinum and 4.0% of the peak free plasma platinum after i.v. infusion. After intracarotid infusion, the mean peak total CSF concentration was 3.4% of the peak total plasma platinum and 7.0% for the peak freeplasma platinum. In patients with meningeal carcinoma-tosis, the mean peak CSF concentrations were 7.7% of the peak total plasma platinum and 13.7% of the peak free plasma platinum. The free to total platinum ratio in plasma decreased quickly and that in CSF increased and was maintained at the high levels of 80% for two hours or more. In patients with a solid metastatic brain tumor, the CDDP concentration in the CSF taken through an Ommaya reservoir placed in the postopera-tive cavity was much higher than that in the CSF taken through an Ommaya reservoir placed in the lateral ven-tricle for both intracarotid and intravenous infusions. In two patients with multiple miliary metastatic brain tumors, CDDP did not enter the CSF even after con-tinuous intracarotid infusion of 10 mg/day for 14 days.}